The proposed studies are designed to evaluate the influence of acid-base disturbances on fluoride metabolism and toxicity in rats and dogs. It has been established that the renal clearance of fluoride, which is the major mechanism for the removal of fluoride from the body, is a direct function of urinary pH. The transport process is best described in terms of the nonionic diffusion of hydrogen fluoride according to the pH gradient across adjacent fluid compartments. Fluoride ion appears to have a limited permeability. Studies concerning the influence of acid-base disturbances on fluoride balance, body fluid fluoride concentrations, fluoride uptake by bones and teeth, and the frequency and severity of dental fluorosis are in various stages of progress. BIBLIOGRAPHIC REFERENCES: Whitford, G.M., Pashley, D.H., and Reynolds, K.E., Fluoride Absorption from the Rat Urinary Bladder: A pH-dependent Event. Am. J. Physiol. 232 (1): 1977. In press. Whitford, G.M., Patten, J.R., Reynolds, K.E. and Pashley, D.H., Blood and Urinary 18F Pharmacokinetics Following Parenteral Administration in the Rat. J. Dent. Res., July-August, 1977. In press.